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Pomen serumskega cistatina C za ugotavljanje okvare ledvic med kemoterapijo
Avtor: Levin Vrhovec
Mentor: doc. dr. Borut Štabuc


Mnoge citotoksicne ucinkovine, ki jih uporabljamo pri zdravljenju raka, lahko okvarijo delovanje ledvic, zato moramo pred in med kemoterapijo redno spremljati njihovo delovanje. Za oceno delovanja ledvic in zgodnjih okvar so najpomembnejši testi ocistkov. V vsakodnevni klinicni praksi delovanje ledvic vrednotimo z ocistkom kreatinina (ECC), saj so preiskave s pomocjo eksogenih oznacevalcev (npr: inulin, 51Cr-EDTA) neprakticne in obremenjujoce za bolnika. Pri dolocanju ECC lahko pride do zavajujocih rezultatov zaradi nedoslednosti bolnika pri zbiranju celodnevnega urina. Da bolnikom ne bi bilo treba zbirati urina, poskušamo ugotoviti enostavnejši in hitrejši nacin ugotavljanja ledvicne funkcije. Cistatin C je serumska beljakovina, ki jo uvršcamo med inhibitorje cisteinskih proteaz. Nastaja v vseh jedrnih celicah. Njegova serumska koncentracija je neodvisna od spola, stanja prehranjenosti, akutnih in kronicnih bolezni ter raka. Ker se v vecini izloca skozi glomerule, njegova serumska koncentracija korelira z glomerulno filtracijo (GFR). Namen naloge je bil ugotoviti, ali koncentracija serumskega cistatina C korelira z GFR oziroma z ECC.
V raziskavi smo analizirali 1l7 vzorcev pri 56 bolnikih. Kreatinin v serumu in urinu smo dolocali z metodo, ki temelji na Jaffe-jevi reakciji, ECC smo izracunali iz volumskega pretoka urina, telesne površine in razmerja med koncentracijo kreatinina v serumu in urinu, cistatin C smo dolocili s turbidimetricno analizno tehniko PET.
Podatke smo statisticno obdelali s programom SimStat. Korelacijske koeficiente smo racunali po Pearson-u v 95% intervalu zaupanja. Pri primerjavi vrednosti serumskega kreatinina in cistatina C smo ugotovili visoko povezanost (r=0.736) za celotno koncentracijsko obmocje. Odnos med vrednostmi cistatina C in ECC je dolocen s korelacijskim koeficientom r=0.792.
Pri 117 vzorcih se je cistatin C razlikoval od ECC v 8 primerih (6.8 %). Metodi se statisticno pomembno ne razlikujeta v deležu patoloških rezultatov (X2=0.86, p=0.35). Zvišana koncentracija cistatina C se ujema z znižanjem ECC v vsaj 93 %.
Raziskava je pokazala, da serumska koncentracija cistatina C lahko z veliko gotovostjo nadomesti dolgotrajno preiskavo ECC pri ugotavljanju zgodnje ledvicne okvare.


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[Abstract / English version]
Serum cystatin C as an kidney failure marker during chemotherapy
Author: Levin Vrhovec
Mentor: doc. dr. Borut Štabuc


Many cytotoxic agents used in antitumor therapies can cause a kidney damage. Therefore there is a necessity for regular kidney function monitoring before and during chemotherapy.
Clearance tests have been proven to be the most accurate indicators for clinical assessment of glomerular filtration (GFR). Because of inconvenience of exogene markers (inulin, 51CrEDTA), endogenous creatinine clearance (ECC) is used in everyday routine work. Results obtained from ECC analysis can often be misleading due to inaccurate urine collecting. In order to avoid the inconvenient urine collecting, we are trying to find an easier and faster way of kidney function assessment.
Cystatin C is a serum protein, which is a member of the cysteine proteinase inhibitors. It is produced by all nucleal cells and its production rate is independent of sex, nutrition status, acute and chronic diseases and cancer. Because it is freely filtered at the glomerulus, its serum concentration correlates with glomerular filtration rate.
The purpose of this research was to find out if the serum cystatin C concentration correlates with GFR and ECC respectively.
We analysed 117 serum samples taken from 56 patients. Serum and urine creatinine concentrations were determined by method based on Jaffe reaction, ECC was calculated from urine flow, surface area and the ratio between serum and urine creatinine concentrations. We used particle enhanced turbidimetric immunoassay (PET) for cystatin C determination.
Data were statistically analysed with Simstat computer program. We used Pearson correlation method with 95 % confidence interval. A good cotrelation coeficient (r=0.736) between the values of serum creatinine and cystatin C was established within the whole concentration interval. The relation between cystatin C and ECC values was determined with correlation coefficient r=0.792.
Cystatin C differed from ECC values in 8 of 117 samples (6.8 %). Methods don't show significant statistical difference in pathological results (X2=0.86, p=0.35). An increased cystatin C concentration corresponds to decreased ECC values in 93 %.
We showed that serum cystatin C concentration can replace with great certainty the ECC method for clinical assessment of esrly kidney damage.